We are developing a structural and chemical data base for the major allergenic epitopes responsible for eliciting type 1 allergic responses. The clinical manifestations of type 1 allergy includes rhinitis, asthma and conjunctivitis, with the large majority of people suffering from type 1 allergy showing sensitivity to the same group of 8-10 proteins. It is a realistic goal to envision the production of a peptide-like mixture of the major epitopes which can be administered to block the initial step in the allergic response and thereby provide a novel therapy for allergy. Using high resolution X-ray crystallography, we have solved the structure of an allergen. In collaboration with Dr. Rudolf Valenta, U. Vienna, we are involved in mapping the epitopes of the profilin which are responsible for binding to surface IgEs and the subsequent receptor clustering events which leads to histamine release. Thus we will have the sequence, the location on the protein, and most importantly, the conformation of the epitope on the allergen. These represent the required data to produce an effective peptide based therapy. As part of our work we have identified a murine monoclonal antibody (moab 4A6) which binds strongly to the epitope Pro-Gln-Phe-Lys-Pro-Gln (residues 42-47) in birch pollen profilin, but does not cross-react with any other plant profilins, all of which have a Glu at position 47 instead of a Gln. the loss of binding may be a consequence of an altered peptide conformation due to the substitution or could arise from unfavorable electrostatic interactions introduced by the Glu at the peptide-antibody interface. We propose to examine the structure of the peptides by solution NMR in order determine whether there is in fact a differences in binding activity. This information will add to our growing data base on the structural and chemical requirements for epitope-based allergy therapies. This work is currently being supported by an NIH grant to S. Almo (GM53807).